TY  - EJOU
AU  - Wang, Yan 
AU  - Zhu, Jialei 
AU  - Wei, Shiyang 
AU  - Jin, Lijie 
AU  - Liu, Zhanqiu 
AU  - Xu, Jie 
AU  - Yang, Nana 
AU  - Jiang, Xuefeng 
AU  - Wang, Caizhi 
AU  - Wang, Lingling 

TI  - Regulation of Histone Emulsification by HPDL via LDHA/LDHB Promotes EC Cell Proliferation
T2  - Oncology Research

PY  - 2026
VL  - 34
IS  - 5
SN  - 1555-3906

AB  -  <b>Background:</b> The role of 4-hydroxyphenylpyruvate dioxygenase-like protein (HPDL) in endometrial cancer (EC) progression remains poorly understood, particularly its involvement in metabolic-epigenetic crosstalk via lactate-driven histone lactylation. This study aimed to investigate HPDL’s mechanistic contribution to EC pathogenesis. <b>Methods:</b> Stable HPDL-overexpressing and knockdown EC cell lines (HEC-1-B and AN3CA) were generated using lentiviral vectors. Functional assays (proliferation, migration, invasion), subcutaneous xenograft models in BALB/c nude mice, and molecular analyses were conducted. Lactate levels, Pan-lysine lactylation (pan-kla), histone H3K18 lactylation (H3K18la), and effects of sodium oxamate (lactate modulator) were assessed. Lactate Dehydrogenase A/Lactate Dehydrogenase B (LDHA/LDHB) knockdown, promoter activity assays, and chromatin immunoprecipitation (ChIP) were performed to evaluate H3K18la occupancy at LDHA/LDHB promoters. <b>Results:</b> HPDL knockdown reduced intracellular lactate, Pan-Kla, and H3K18la levels, while overexpression elevated these markers. Sodium oxamate amplified lactate and lactylation in HPDL-overexpressing cells but suppressed histone lactylation independently of HPDL. LDHA/LDHB knockdown diminished lactylation, repressed HPDL expression, and inhibited promoter activity. ChIP revealed H3K18la enrichment at LDHA/LDHB promoters in HPDL-overexpressing cells and reduced occupancy in knockdown models. HPDL enhanced EC cell proliferation, migration, and invasion <i>in vitro</i>. <i>In vivo</i>, HPDL-overexpressing xenografts exhibited accelerated tumor growth and larger volumes compared to controls. <b>Conclusions:</b> HPDL regulates histone lactylation via LDHA/LDHB and promotes the proliferation of EC cells.
KW  - Endometrial cancer; histone lactylation; 4-hydroxyphenylpyruvate dioxygenase-like protein; lactate dehydrogenase A/B; cell proliferation

DO  - 10.32604/or.2026.068833